Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “evolvability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2005

A randomized, double-blind, placebo-controlled study of the safety and efficacy of intravenous MCC-135 as an adjunct to primary percutaneous coronary intervention in patients with acute myocardial infarction: rationale and design of the evaluation of MCC-135 for left ventricular salvage in acute MI (EVOLVE) study.

As a consequence of acute ischemia and reperfusion in patients with acute ST elevation myocardial infarction, calcium overload inside myocytes not only affects myocardial contraction, relaxation, and myocyte recovery following reperfusion, but also may be related to myocyte necrosis and fatal arrhythmia. MCC-135 is the first in a new class of agents that reduce intracellular calcium overload. Pre-clinical and early clinical studies yielded promising results for patients with ST elevation myocardial infarction. The Evaluation of MCC-135 for Left Ventricular Salvage in Acute MI (EVOLVE) study is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled clinical trial of 2 new doses of MCC-135 (4.5 mg/kg/48 hours and 9.0 mg/kg/48 hours) as adjunct therapy for preservation of left ventricular function and reduction of infarct size in patients undergoing primary percutaneous coronary intervention (PCI) for electrocardiographically moderate-large ST elevation myocardial infarction. The primary endpoint will be left ventricular ejection fraction on Day 5 post myocardial infarction as determined by single photon emission computed tomography (SPECT). Secondary endpoints will include SPECT and echocardiographic assessments, serum cardiac markers, clinical outcomes, and safety measures at specific time points through Day 30 post myocardial infarction. Follow-up clinical and safety assessments will be continued until Day 180. The rationale, design, and methods of the EVOLVE study are described in this paper, along with 2 sub-studies, involving a comparison of pre- and post-PCI measurements with either SPECT or echocardiography, to examine myocardial salvage and the time course of changes in myocardial infarction size and left ventricular function. MINIABSTRACT: The Evaluation of MCC-135 for Left Ventricular Salvage in Acute MI (EVOLVE) study is a Phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial of two doses of MCC-135, first in a new class of agents that reduce intracellular calcium overload, as adjunct therapy for preservation of left ventricular function and reduction of infarct size in patients with moderate-large STEMI undergoing primary PCI. The rationale, design, and methods of the EVOLVE study, along with two sub-studies, are described in this paper.

Acute Disease↗
PubMed1985

The role of chloride ion on the photoreactivation of the oxygen-evolving center of tris-washed, 2,6-dichlorophenol indophenol-treated grana.

Chloride ion is found to be an essential factor in photoreactivation of the oxygen-evolving center. Tris-washed, 2,6-dichlorophenol indophenol-treated grana are low in both Mn content and oxygen-evolving activity. These grana can restore high oxygen-evolving activity, however, by incorporating Mn2+ ion under weak light in the presence of chloride and calcium ions with dithiothreitol. This restoration is called photoreactivation. When chloride ion is omitted from the medium for the photoreactivation, the recovery of oxygen-evolving activity is inhibited. Other anions, such as bromide and nitrate anions, could also mediate the reactivation; but, anions of weak acids or polyvalent strong acids were not effective. Chloride ion is also required in the light-induced H+ and Mn2+ uptake of these grana, which are essential partial reactions for the reactivation. It is therefore concluded that chloride ion plays an important role in the photoreactivation.

2,6-Dichloroindophenol↗
PubMed1993

The relationship between the capacity to evolve oxygen and the variable fluorescence of chlorophyll after microsecond illumination in Chlorella, pea leaves and pea thylakoids.

The relationship between the capacity to evolve oxygen following a flash of a few microseconds duration and the variable fluorescence of chlorophyll was determined in Chlorella, leaf disks of peas, and thylakoids of pea leaves. It was found that this relationship is linear in intact plant material, while it is nonlinear in thylakoids. However, in thylakoids, the recovery of the capacity to evolve oxygen does not track the decay of the variable yield of Chl a fluorescence. This nonlinear relationship in thylakoids results from a reduced rate in the oxygen evolution reaction with no change in the decay of the variable yield of Chl a fluorescence. From a new application of the matrix analysis method to oxygen flash yields, the S1'-->S2, S2'-->S3 and S3'-->S4-->S0 transitions are found to be slowed or delayed in pea thylakoids and this underlies the slower rate of the recovery of the capacity to evolve oxygen in thylakoids. It is concluded that in intact cells the QA-QB(-)-->QA QB- reaction was rate-limiting for the recovery of the capacity to evolve oxygen, the equal energy-transfer hypothesis and the sequential double-hit model are valid in pea leaves and that the apparent invalidity in thylakoids is actually due to slowing of reaction steps in the oxygen evolution mechanism.

Chlorella↗
PubMed1994

Identification of chicken GnRH II in brains of metatherian and early-evolved eutherian species of mammals.

Two molecular forms of GnRH (chicken GnRH II and a second variant) are present in the brains of species from all the major vertebrate groups. In mammals, two forms are present in metatherian species and early-evolved eutherian species, but chicken GnRH II has not been identified in more advanced eutherian species. We investigated the nature of GnRH molecular forms in several early-evolved mammalian species, using high performance liquid chromatography and radioimmunoassay with specific GnRH antisera. These chromatographic and immunological data indicate that in the brains of a metatherian species (possum, Trichosurus vulpecula) and in two early-evolved eutherian species (order Insectivora: musk shrew, Suncus murinus and mole, Chrysochloris asiatica), both mammalian and chicken II GnRHs are present, while in another relatively early-evolved eutherian species (order Chiroptera: bat, Miniopterus schreibersii) only mammalian GnRH is present. In the adult possum and mole brains the proportion of chicken GnRH II was lower than that of mammalian GnRH, while in the musk shrew brain chicken GnRH II predominated. A peptide likely to be mammalian proGnRH was detected in the brains of the three eutherian species (musk shrew, mole, and bat). These findings suggest that metatherian and primitive eutherian species of mammals continue to express chicken GnRH II as in the vast majority of nonmammalian vertebrates, while the peptide is apparently not expressed in modern placental mammalian species. The functional significance of chicken GnRH II is not yet clear, but there are indications that it has a neurotransmitter or neuromodulator role in addition to that of regulating pituitary hormone release in certain vertebrate species.

Animals↗
PubMed2004

A hydrogen-evolving enzyme is present in Frankia sp. R43.

The ability to evolve hydrogen using methyl viologen as an electron donor was assayed in the nitrogen-fixing actinomycetes Frankia sp. R43 and Frankia sp. KB5. To further examine the nature of hydrogen-evolving enzymes that may be present in these organisms immunological studies were performed. Under anaerobic conditions (both nitrogen-limiting and nitrogen-containing) Frankia sp. R43 but not Frankia sp. KB5 evolved hydrogen,which was not linked to NAD-reducing activity. Immunological analysis of total protein from Frankia sp. R43 and Frankia sp. KB5 using an antiserum raised against Ralstonia eutropha HoxF, recognized an antigen in Frankia sp. R43 but not in Frankia sp. KB5. Immunogold labeling using antibodies raised against the R. eutropha HoxH recognized sites in both hyphae and vesicles of Frankia sp. R43, but not in Frankia sp. KB5. Based on these physiological and immunological findings, we conclude that Frankia sp. R43 has a hydrogen-evolving hydrogenase.

Anaerobiosis↗
PubMed2004

Strong altruism can evolve in randomly formed groups.

Although the conditions under which altruistic behaviors evolve continue to be vigorously debated, there is general agreement that altruistic traits involving an absolute cost to altruists (strong altruism) cannot evolve when populations are structured with randomly formed groups. This conclusion implies that the evolution of such traits depends upon special environmental conditions or additional organismic capabilities that enable altruists to interact with each other more than would be expected with random grouping. Here we show, using both analytic and simulation results, that the positive assortment necessary for strong altruism to evolve does not require these additional mechanisms, but merely that randomly formed groups exist for more than one generation. Conditions favoring the selection of altruists, which are absent when random groups initially form, can naturally arise even after a single generation within groups-and even as the proportion of altruists simultaneously decreases. The gains made by altruists in a second generation within groups can more than compensate for the losses suffered in the first and in this way altruism can ratchet up to high levels. This is true even if altruism is initially rare, migration between groups allowed, homogeneous altruist groups prohibited, population growth restricted, or kin selection precluded. Until now random group formation models have neglected the significance of multigenerational groups-even though such groups are a central feature of classic "haystack" models of the evolution of altruism. We also explore the important role that stochasticity (effectively absent in the original infinite models) plays in the evolution of altruism. The fact that strong altruism can increase when groups are periodically and randomly formed suggests that altruism may evolve more readily and in simpler organisms than is generally appreciated.

Altruism↗
PubMed2005

The role of epistatic gene interactions in the response to selection and the evolution of evolvability.

It has been argued that the architecture of the genotype-phenotype map determines evolvability, but few studies have attempted to quantify these effects. In this article we use the multilinear epistatic model to study the effects of different forms of epistasis on the response to directional selection. We derive an analytical prediction for the change in the additive genetic variance, and use individual-based simulations to understand the dynamics of evolvability and the evolution of genetic architecture. This shows that the major determinant for the evolution of the additive variance, and thus the evolvability, is directional epistasis. Positive directional epistasis leads to an acceleration of evolvability, while negative directional epistasis leads to canalization. In contrast, pure non-directional epistasis has little effect on the response to selection. One consequence of this is that the classical epistatic variance components, which do not distinguish directional and non-directional effects, are useless as predictors of evolutionary dynamics. The build-up of linkage disequilibrium also has negligible effects. We argue that directional epistasis is likely to have major effects on evolutionary dynamics and should be the focus of empirical studies of epistasis.

Biological Evolution↗
PubMed2004

Stability and the evolvability of function in a model protein.

Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to evolve the function of binding to a ligand. Although our model contains no built-in tradeoff between stability and function, proteins evolved function more efficiently when the stability requirement was relaxed. Proteins with both high stability and high function evolved more efficiently when the stability requirement was gradually increased than when there was constant selection for high stability. These results show that in our model, the evolution of function is enhanced by allowing proteins to explore sequences corresponding to marginally stable structures, and that it is easier to improve stability while maintaining high function than to improve function while maintaining high stability. Our model also demonstrates that even in the absence of a fundamental biophysical tradeoff between stability and function, the speed with which function can evolve is limited by the stability requirement imposed on the protein.

Biophysics↗
PubMed2002

Sequentially evolved bilateral epidural haematomas.

Sequentially evolved bilateral epidural haematomas, where the second haematoma evolves after surgical removal of the first haematoma, are rarely reported. We report two cases of this entity. One patient was involved in a road traffic accident and the other was suffering from a head injury after an assault. CT scans showed that both patients had an unilateral epidural haematoma with a thin presumably epidural haemorrhage on the opposite side. Both patients were operated for their epidural haematomas, but did not improve after surgical treatment, and postoperative CT scans revealed evolving of an epidural haematoma on the opposite side. After evacuation of the second epidural haematoma both patients recovered quickly. Sequentially evolved bilateral epidural haematomas are rare, but must be considered in the postoperative intensive care treatment in patients with epidural haematomas. Both cases emphasize the need for intensive care monitoring after an operation for an epidural haematoma and the need for CT scans if the patient does not improve quickly after removal of the haematoma. This is especially important if a small contralateral haematoma is seen on the initial CT scan.

Adult↗
PubMed1997

Early and late outcome after CABG in patients with evolving myocardial infarction.

OBJECTIVE: To study the determinants of early and late outcome after coronary artery bypass grafting (CABG) for evolving myocardial infarction. METHOD: 269 consecutive patients underwent isolated primary or repeat CABG from 1971 to 1992 for evolving myocardial infarction. By institutional policy, these were patients, strictly diagnosed, infarcting either in the cardiac cateterization laboratory, shortly after a previous CABG, or on cardiac intervention waiting lists. At operation, 125 patients were hemodynamically stable, 89 patients in cardiogenic shock 55 patients in cardiopulmonary resuscitation (CPR). Interval between infarct onset and surgical reperfusion ranged from 53 min to 15 h (median, 135 min; 90% between 75 and 360). An internal mammary artery graft (IMA) was used in 81 patients. Cross-sectional follow-up was 100% complete and multivariable analysis was conducted in the hazard function domain. RESULT: One-month, 1-year and 10-year survival was 86, 84 and 66%, respectively. The 1-year and 10-year survival, stratified by hemodynamic class, was respectively 98 and 77% for the stable patients, 77 and 60% for the patients in shock and 62 and 49% for those undergoing CPR. Shock and CPR were incremental risk factors for early but not late risk. Use of an IMA graft was not a risk factor early or late in either stable or unstable patients. CONCLUSION: CABG can be performed with acceptable early and long-term risk in selected patients with evolving myocardial infarction, whatever their hemodynamic state. Outcome as regards survival is neither adversely or advantageously affected by choice of bypassing conduit. An evolving myocardial infarction with stable hemodynamics carries a lesser risk than an unstable anginal state with changing ST-segment.

Angina, Unstable↗
PubMed2001

Stuck in the pleistocene: rationality and evolved social roles.

This article argues that an evolutionary psychological perspective could be useful for developing second-generation models of rationality. The standard model of complete rationality is inadequate primarily on the grounds that it generates predictions inconsistent with empirical data. The model is extremely useful and should not, nor cannot, realistically be dismissed. It accurately predicts outcomes in markets and openly competitive situations. However, behavioral phenomena that the standard theory has trouble explaining -- such as mass contribution to public goods, types of cooperation, and altruism -- are usually treated as "anomalies." These outcomes are too prevalent and important to be treated as such. I attempt to build upon Elinor Ostrom's proposal to generate new models of rationality, which recognize the use of heuristics, norms, and rules, and are able to better account for empirical findings. I argue that second-generation models would benefit from the acknowledgment of social roles -- but more specifically, evolved social roles. Evolved social roles are intuitive bundles of norms, expectations, and social strategies that shape an individual's player type. If we extend rationality to incorporate underlying biopsychological mechanisms, such as evolved social strategies and evolved social roles, then we gain an understanding of a wider array of decision-making processes and social phenomena.

Journal Article↗
PubMed1994

Biochemical and spectroscopic characterization of a new oxygen-evolving photosystem II core complex from the cyanobacterium Synechocystis PCC 6803.

We describe here a new procedure permitting rapid (12-13 h) isolation of a pure oxygen-evolving photosystem II (PSII) core complex from the cyanobacterium Synechocystis PCC 6803. This procedure involves dodecyl maltoside extraction of thylakoid membranes followed by single-step column chromatography using a weak anion-exchanger. SDS-PAGE and immunoblotting show that the complex consists of five intrinsic membrane proteins (CP47, CP43, D1, D1, and cyt b559), one extrinsic protein (MSP), and one unknown protein with a molecular mass of approximately 26 kDa. A chemical and functional analysis, normalized to 2 molecules of pheophytin a, indicates that this PSII core complex contains 1 photoactive plastoquinone, QA, 4 manganese atoms, 38 chlorophyll a molecules, 1 cytochrome b559, 2 plastoquinone-9, and 9-10 beta-carotenes. The complex exhibits high rates of oxygen evolution, typically 2400-2600 mumol of O2 (mg of Chl)-1 h-1 in the presence of 2,5-dichlorobenzoquinone as an artificial electron acceptor with a pH optimum of 6.5. A strong light minus dark multiline EPR signal, arising from the S2 state of the oxygen-evolving complex (OEC), is observed at 10 K following illumination at 198 K. The determination of the absolute oxygen yield per saturating microsecond flash indicates that essentially all of the PSII centers contain functional oxygen-evolving complexes. This point is further supported by the absence of photoaccumulation, upon room temperature illumination, of the immediate oxidant of the OEC, redox-active tyrosine, YZ.. On the basis of EPR spectra, oxidized minus reduced difference spectra, and SDS-PAGE, the preparation contains on a per mole basis with PSII only trace amounts of PSI (approximately 0.04), cytochrome b6/f complex (< or = 0.01), and ATPase (< or = 0.05). All of these results indicate that this PSII preparation is to date the most highly purified oxygen-evolving core complex from Synechocystis 6803 that retains all of the reaction centers active for oxygen evolution. As Synechocystis 6803 is being used extensively for site-directed mutagenesis of PSII, this preparation is particularly valuable for spectroscopic and biochemical analyses of PSII from wild-type and from site-directed mutants.

Calcium↗
PubMed2002

Calcium depletion modifies the structure of the photosystem II O(2)-evolving complex.

A 5 min exposure of photosystem II to a pH 3 citric acid solution is a simple method for selective removal of Ca(2+) from the O(2)-evolving complex. The resulting preparation retains the 23 and 17 kDa extrinsic polypeptides, but the activity of this material is only 10-20% of that of an untreated control sample. Biochemical characterization of citrate-treated photosystem II reveals that some reaction centers lose the extrinsic proteins during citrate treatment. Furthermore, a comparison of photosystem II preparations treated with citrate, or depleted of 23 and 17 kDa extrinsic polypeptides by high-salt treatment, shows that low concentrations of a small reductant, NH(2)OH, which has little effect on the activity of intact photosystem II, can reduce and inhibit the Mn cluster in both types of preparations. In contrast, a large reductant, hydroquinone, cannot access the majority of O(2)-evolving centers in citrate-treated preparations, while 23 and 17 kDa-depleted material is rapidly inactivated by the reductant. Incubation of the citrate-treated samples in high ( approximately 60 mM) concentrations of CaCl(2) restores 50% of the lost activity; this Ca(2+)-reconstituted activity is chelator-insensitive, indicating that rebinding of Ca(2+) restores the structural integrity of the O(2)-evolving complex. A characterization of Ca(2+) and Cl(-) affinities in steady-state activity assays shows that citrate-treated preparations exhibit a Cl(-) requirement similar to that of polypeptide-depleted photosystem II, while Ca(2+) reactivation of O(2) evolution appears to occur at two structurally distinct sites. One site exhibits a high Ca(2+) affinity, similar to that found in polypeptide-depleted samples, but a second, lower-affinity site also exists, with a K(M) that is approximately 10 times greater than that of the high-affinity site, which is associated with centers that retain the extrinsic polypeptides. These data indicate that citrate-induced Ca(2+) depletion causes release of the 23 and 17 kDa extrinsic polypeptides from some photosystem II reaction centers, and also modifies the structure of the polypeptide-retaining O(2)-evolving centers so that the Mn cluster is exposed to small, but not large, reductants. This change may be due to subtle modifications to the structure of the photosystem II extrinsic proteins that produces a new pathway between the solvent and the Mn cluster or, alternatively, to the opening of an existing channel in the intrinsic lumenal polypeptide domain, between the solvent and the Mn cluster, that is normally occluded by a bound Ca(2+) atom.

Calcium↗
PubMed2005

Reduction-induced inhibition and Mn(II) release from the photosystem II oxygen-evolving complex by hydroquinone or NH2OH are consistent with a Mn(III)/Mn(III)/Mn(IV)/Mn(IV) oxidation state for the dark-adapted enzyme.

Hydroxylamine and hydroquinone were used to probe the oxidation states of Mn in the oxygen-evolving complex of dark-adapted intact (hydroxylamine) and salt-washed (hydroquinone) photosystem II. These preparations were incubated in the dark for 24 h in the presence of increasing reductant/photosystem II ratios, and the loss of oxygen evolution activity and of Mn(II) was determined for each incubation mixture. Monte Carlo simulations of these data yielded models that provide insight into the structure, reactivity, and oxidation states of the manganese in the oxygen-evolving complex. Specifically, the data support oxidation states of Mn(III)(2)/Mn(IV)(2) for the dark stable S(1) state of the O(2)-evolving complex. Activity and Mn(II) loss data were best modeled by assuming an S(1) --> S(-)(1) conversion of intermediate probability, a S(-)(1) --> S(-)(3) reaction of high probability, and subsequent step(s) of low probability. This model predicts that photosystem II Mn clusters that have undergone an initial reduction step become more reactive toward a second reduction, followed by a slower third reduction step. Analysis of the Mn(II) release parameters used to model the data suggests that the photosystem II manganese cluster consists of three Mn atoms that exhibit a facile reactivity with both reductants, and a single Mn that is reducible but sterically trapped at or near its binding site. Activity assays indicate that intact photosystem II centers reduced to S(-)(1) can evolve oxygen upon illumination, but that these centers are inactive in preparations depleted of the extrinsic 23 and 17 kDa polypeptides. Finally, it was found that a substantial population of the tyrosine D radical is reduced by hydroxylamine, but a smaller population reacts with hydroquinone over the course of a 24 h exposure to the reductant.

Adaptation, Physiological↗
PubMed1999

Tyrosine-Z in oxygen-evolving photosystem II: a hydrogen-bonded tyrosinate.

In oxygen-evolving photosystem II (PSII), a tyrosine residue, D1Tyr161 (YZ), serves as the intermediate electron carrier between the catalytic Mn cluster and the photochemically active chlorophyll moiety P680. A more direct catalytic role of YZ, as a hydrogen abstractor from bound water, has been postulated. That YZox appears as a neutral (i.e. deprotonated) radical, YZ*, in EPR studies is compatible with this notion. Data based on electrochromic absorption transients, however, are conflicting because they indicate that the phenolic proton remains on or near to YZox. In Mn-depleted PSII the electron transfer between YZ and P680+ can be almost as fast as in oxygen-evolving material, however, only at alkaline pH. With an apparent pK of about 7 the fast reaction is suppressed and converted into an about 100-fold slower one which dominates at acid pH. In the present work we investigated the optical difference spectra attributable to the transition YZ --> YZox as function of the pH. We scanned the UV and VIS range and used Mn-depleted PSII core particles and also oxygen-evolving ones. Comparing these spectra with published in vitro and in vivo spectra of phenolic compounds, we arrived at the following conclusions: In oxygen-evolving PSII YZ resembles a hydrogen-bonded tyrosinate, YZ(-).H(+).B. The phenolic proton is shifted toward a base B already in the reduced state and even more so in the oxidized state. The retention of the phenolic proton in a hydrogen-bonded network gives rise to a positive net charge in the immediate vicinity of the neutral radical YZ*. It may be favorable both for the very rapid reduction by YZ of P680+ and for electron (not hydrogen) abstraction by YZ* from the Mn-water cluster.

Hydrogen Bonding↗
PubMed2006

Control of transcription factor activity and osteoblast differentiation in mammalian cells using an evolved small-molecule-dependent intein.

Inteins are naturally occurring protein elements that catalyze their own excision from within a larger protein together with the ligation of the flanking "extein" sequences. Previously we reported the directed evolution of an intein-based molecular switch in which intein splicing in yeast cells was made dependent on the cell-permeable small molecule 4-hydroxytamoxifen (4-HT). Here we show that these evolved inteins are effective means of rendering protein function and biological signaling pathway activation dependent on 4-HT in mammalian cells. We have characterized the generality, speed, and dose dependence of ligand-induced protein splicing in murine NIH3T3 cells and in human HEK293 cells. Evolved inteins were used to control in mammalian cells the function of Gli1 and a truncated form of Gli3, two transcriptional mediators of the Hedgehog signaling pathway. Finally, we show that a complex biological process such as osteoblast differentiation can be made dependent on 4-HT using the evolved intein system. Our findings suggest that evolved small-molecule-dependent inteins may serve as a general means of achieving gene-specific, dose-dependent, post-translational, and small-molecule-induced control over protein activity in mammalian systems.

Animals↗
PubMed1998

A proposed path by which genes common to mammalian X and Y chromosomes evolve to become X inactivated.

Mammalian X and Y chromosomes evolved from an autosomal pair; the X retained and the Y gradually lost most ancestral genes. In females, one X chromosome is silenced by X inactivation, a process that is often assumed to have evolved on a broadly regional or chromosomal basis. Here we propose that genes or clusters common to both the X and Y chromosomes (X-Y genes) evolved independently along a multistep path, eventually acquiring dosage compensation on the X chromosome. Three genes studied here, and other extant genes, appear to be intermediates. ZFX, RPS4X and SMCX were monitored for X inactivation in diverse species by assaying CpG-island methylation, which mirrors X inactivation in many eutherians. ZFX evidently escaped X inactivation in proto-eutherians, which also possessed a very similar Y-linked gene; both characteristics were retained in most extant orders, but not in myomorph rodents. For RPS4X, escape from X inactivation seems unique to primates. SMCX escapes inactivation in primates and myomorphs but not in several other lineages. Thus, X inactivation can evolve independently for each of these genes. We propose that it is an adaptation to the decay of a homologous, Y-linked gene.

Animals↗
PubMed2004

Acute effects of inhaled nitric oxide on pulmonary and cardiac function in preterm infants with evolving bronchopulmonary dysplasia.

BACKGROUND: Inhaled nitric oxide (iNO) reduces pulmonary vascular resistance by preferential vasodilation in ventilated lung units. In experimental animals, iNO also reduces airway resistance by smooth muscle relaxation. Hence, there may be a therapeutic role for iNO in evolving bronchopulmonary dysplasia (BPD). OBJECTIVE: To evaluate the acute effects of low-dose iNO on lung mechanics, ventilation distribution, oxygenation, and cardiac function in preterm infants with evolving BPD. METHODS: Measurements of lung compliance (C(L)), airway resistance (R(L)), ventilation-distribution (N(2) clearance in multiple-breath washout), oxygenation (SpO(2)), left ventricular ejection fraction (LVEF) and right ventricular shortening fraction were obtained before and during 2 hours of iNO (10 ppm) in a group of ventilated preterm infants with evolving BPD. RESULTS: A total of 13 preterm infants with (mean+/-SD) BW: 663.8+/-116 g, GA: 24.9+/-1.2 weeks, age: 32+/-14 days, mean airway pressure: 6.7+/-0.9 cmH(2)O and fraction of inspired oxygen: 0.35+/-0.06 were studied. iNO did not affect C(L), R(L) or N(2) clearance. There was a small increase in LVEF. Mean SpO(2) remained unchanged, but the duration of spontaneous hypoxemic episodes increased during iNO. CONCLUSION: Low-dose iNO had no acute effects on lung function, cardiac function and oxygenation in evolving BPD.

Administration, Inhalation↗